| The study is a part of "Essential study of the property of TCM base on three factors theory", which is supported by the Major State Basic Research Development Program of China(National Project 973)(No.2007CB512605). The property theory of TCM is the basic and guideline of TCM applications in clinic.The study focuses on investigating the factors of the formation and expression of the property of TCM. A hypothesis is proposed that the property of TCM derives from its bioactivity, which is related to the status of organism and chemical constituents. Therefore, the status of organism, chemical constituents and bioactivity are considered to be three factors of the property of TCM. The organism plays a role in expression of bioactivity of drugs. This study is searching for physiological indexes characterizing the status of organism and mechanism of bioactivity of drugs in different organism status. Cortex Cinnamomi is pungent and sweet in taste and hot in nature, the channels tropism arekidney, liver, heart and spleen.As an important "hot properly" drug, thestudy of in vivo metabolism of Cortex Cinnamon in different organism status will provide some foundations to understand the property of TCM.Cortex Cinnamon,the dried cortex of Cinnamomum cassia Presl of Lauraceae, It is pungent and sweet in taste and hot in nature, the channels tropism are kidney, liver, heart and spleen. Cortex Cinnamon is of great curative power in relieving internal cold or ache or weakness conduced by cold. It has been reported to contain volatile oil, flavanol and its polymersomes, diterpene compounds,tannin etc. The studies about Cortex Cinnamon mostly focus on chemicalcomponents and pharmacological effects at present, the study of its metabolism in vivo focus on Chinese herbal compound. This paper intends to discuss if there are some differences among different status organisms induced by the same component in the same plant.Part one:made cinnamon oil and checked out the stability of extract by HPLC. The results showed that the cinnamon oil was stabile in 3 weeks.The cinnamaldehyde content was 82.86%of cinnamon oil by GC-MS.Part two:determined th at cinnamic acid w as one of the main components inplasma from cinnamon oil; detected the concentrations of cinnamic acid in rat tissues, the results showed that cinnamic acid could be detected in blood, heart, liver,spleen,lung, kidney and brain, but the concentrations of cinnamic acid in brain could not reach the limit of quantification; determined that this paper would research the pharmacokinetics process and tissue distribution of cinnamaldehyde among different organism status.Part three:evaluated the method that detect the concentrations of cinnamic acid in blood, heart, liver, spleen, lung, kidney, the results showed that determined method had good linear relationship and good accuracy and precision; the sample was stabile in 12 hours,7 days and 20 days at room temperature,-20℃,-80℃respectively;the limit of detection was 1.2ng(S/N≥3)and the limit of quantification was 4ng(S/N≥10); Cinnamaldehyde was administered to normal rats, converted into cinnamic acid quickly and reached the maximal plasma level rapidly, it was eliminated in 3 hours from blood and eliminated quickly from tissues, but the maintaining time in lung longer than that in other tissues and the blood concentration in lung higher than that in other tissues.Part four:discussed the differences of pharmacokinetics parameters between normal rats, deficiency-cold syndrome rats and deficiency heat syndrome rats afteradministration cinnamaldehyde orally; established deficiency-cold model rats by injected hydrocortisone for two weeks; established deficiency heat model rats by injected dexamethasone for two weeks and established normal rats by injected normal saline for two weeks; taken blood and tissues at different time points after single administration cinnamaldehyde orally;drawn concentration-time curve; The pharmacokinetic parameters were assessed by non-compartmental method using DAS 2.1.1,there were differences in AUC(0-t),AUMC(0-t),MRT(0-t),t1/2Z-VZ/F,CLZ/F between normal rats and model rats; the results showed that the absorption in deficiency-cold model rats was less than that in normal rats,and the elimination rate was faster than the normal group; the absorption in deficiency heat model rats was less than that in normal rats, but the elimination rate was not significant differences from normal rats.The tissue distribution of cinnamic acid in normal rats was:lung>liver>kidney>spleen>heart; The tissue distribution of cinnamic acid in deficiency-cold sy-ndrome rats was:(liver, lung)>kidney>spleen>heart; The tissue distribution ofcinnamic acid in deficiency heat syndrome rats was:lung>spleen>kidney>liver>heart. The results showed that there were some differences in the pharmacokinetics process and tissue distribution ofcinnamic acid among different organism status.The results of this paper could be summarized as follows:(1) cinnamic acid was one of the main components in plasma from cinnamon oil; (2) this paper checked out the pharmacokinetics process and tissue distribution of the components in plasma from cinnamaldehyde,the results showed that there were some differences in the pharmacokinetics process and tissue distribution of cinnamic acid among different organism status;(3)this paper established the determine method of cinnamic acid in vivo by HPLC. |
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